Quaternary salts of triphenylethanols, -ethylenes, and -ethanes



United States Patent QUATERNARY SALTS 0F TRIPHENYLETHANOLS, -ETHYLENES, AND -ETHANES Frank Patrick Palop'oli, Cincinnati, Ohio, Robert Edward Allen, Walnut Creek, Califl, Edward Lewis Schumann, Kalamazoo, Mich., and Marcus George Van Campen, Berkeley, Calif assignors to The Wm. S. Merrell Company, Cincinnati, Ohio, a corporation of Delaware No Drawing. Filed Oct. 21, 19 59, Ser. No. 847,700

7 Claims. (Cl. 260294.7)

This invention relates to new chemical compounds which possess useful physiological and other valuable properties.

The new compounds of the present invention are quaternary ammonium derivatives of the formula wherein R and R are lower alkyl radicals, or R and R may be joined together with N atom to form a saturated heterocyclic amino radical such as piperidino, pyrrolidino, or morpholino, R is a lower alkyl group, X is an anion such as halogen, sulfate, methosulfate, or toluenesulfonate, 'n is an integer from 2 to 3, (Y) is an ethane ((IJCHZ) group, and R and R are hydrogen, lower alkyl, lo-wer alkoxyl, halogen or perfluorinated alkyl radicals, but both R, and R cannot be hydrogen.

The novel compounds of this invention may be prepared by quaternizing a basic compound of the formula wherein R R n, (Y), R and R are the same as above, with a quaternizing agent of the formula wherein R and X are the same as above.

The substituted basic triphenylethanols, -ethylenes, and -ethancs may "be prepared according to the procedure described in our respective eopending applications, Serial Numbers 676,478, and 676,494, and 676,477, filed August 6, 1957, which have issued as Patent Nos. 2,914,- 562; 2,914,564 and 2,914,561 respectively.

The new compounds of the present invention have been found to possess valuable cardiovascular properties which produce a hypotensive response up'on administration to animals. The new compounds are, therefore, useful in the treatment of hypertension and peripheral vascular disease. The new compounds also have other valuable 2,971,001 Patented Feb. 7, 1961 1 [p-(fl-diethylaminoethoxy phenyl] (p-tolyl) Z-(p-chlorophenyl ethanol ethobromide To 10 g. (0.023 mole of 1[p-(p-diethylaminoethoxyy phenyl]-1-(-ptolyl)-2-(p-chlorophenyl)ethanol in ml. of anhydrous benzene was added 5 ml. of ethyl bromide. The solution was refluxed for 2 days during which time a While solid separated. The precipitated solid was recrystallized f-rom a mixture of isopropyl alcohol and ethyl acetate to give 6.0 g. of the desired 1-[p-( ,B-diethylaminoethoxy)phenyl]-1-(p-tolyl) 2 (p-chlorophenyl)ethanol ethobromide which decomposed at 202 C.

EXAMPLE II 1- [p- (B-diethylaminoethoxy)phenyl] -1-phenyl-2- (p-m'eth0xyphenyl)ethan0l ethobromide To 8.2 g. (0.02 mole) of 1-[p-(B-diethylaminoethoxy)- phenyl]-1-phenyl-2-(p-methoxyphenyl)ethanol in 100 ml. of chloroform was added 3.3 g. (0.03 mole) of ethyl bromide. The solution was refluxed for 3 hours and the solvent removed. The residue was crystallized from a mixture of isopropyl alcohol and diethyl ether to give the desired 1- [p-( B-diethylaminoethoxy) phenyl -1-phenyl-2- (p-methoxyphenyl)ethanol ethobromide, which decomposed at 93 C.

EXAMPLE III 1- [p-(B-dimethylaminoethoxy)phenyl] -1-(p-t0lyl) 2 p-chlorophenyl ethanol methobromide To 4.1 g. (0.01 mole) of l-[p-({3-dimethylaminoethoxy)phenyl]-1-(p-tolyl)-2-(p-chlorophenyl)ethanol in 50 ml. of methanol was added 2.5 ml. of 70% methanolic methyl bromide. The reaction mixture stood at room temperature for 72 hours and then was diluted with ethyl acetate causing a white crystalline solid to separate. After recrystallization from a methanol-ethyl acetate mixture there was obtained the desired l-[p-(B-dimethylaminoethoxy) phenyl]-1-(p-tolyl) 2-(p-chlorophenyl9 ethanol methobromide which melted with decomposition at C.

EXAMPLE IV 1- [p-(B-diethylaminoethoxy phenyl] -1-(p-t0lyl) -2- (p-chlorophenyl)ethan0l methyl p-toluenesulfonate When the procedure of Example I was followed using 1 [p-(fl-diethylaminoethoxy)phenyl] l-(p-tolyl)-2-(pchlorophenyl)ethanol and methyl p-toluenesulfonate, the desired 1-[p-(fi-diethyl-aminoiethoxy)phenyl] -l-(p-tolyl) Z-(p-chlorophenyl ethanol methyl p-toluenesulfonate was obtained as a dihydrate melting at 84-86 C.

EXAMPLE V l-[p-(-y-piperidinopr0p0xy)phenyl1- 1 '(p-chlorophenyly 2-(p-t0lyl)ethanol methobromide When the procedure of Example III was followed using 1 [p- ('y-piperidinopropoxy)-phenyl] 1-(p-chlorophenyl)-2-(p-tolyl)eth-anol and methyl bromide, the desired 1 [p-(v'piperidinopropoxy)phenyl] 1 (p-chlorophenyl)-2-(p-tolyl)ethanol methobromide was obtained as a white solid melting at -196" C.

3 EXAMPLE v1 When 1 [p-(B-diethylarninoethoxy)phenyl] l-(p-trifiuoromethylphenyl) -2-(p-chloropheny1) ethanol replaced the ethanol in the procedure of Example I, there was obtained 1- [p-(fi-diethylaminoethoxy) phenyl] -1-(p-trifluoromethylphenyl)-2 (p-chlorophenyl)-ethanol ethobrornide which melted at 193 C. with decomposition.

EXAMPLE VII 1- [p-(fi-diethylaminoethoxy)phenyl] -1- (p-tolyl) -2- (p-chlorophenyl) ethylene etlzobrom ide When 1 [p-(B-diethylaminoethoxy)phenyl] -l-(p-tol-yl) Z-(p-chlorophenyl)ethylene replaced the ethanol of Example 1 there was obtained the desired l-[p-(fi-diethylaminoethoxy)phenyl] l-(p-tolyl)-2 p-cl1loropheny1)ethylene ethobromide which melted at 215-217 C.

EXAMPLE VIII 1- [p- (B-d'iethylaminoethoxy)phenyl] -1-phenyl-2- (p -methoxyphenyl) ethylene methobromide When the procedure of Example III was followed using 1 [p-(e-diethylarninoethoxy)phenyl] -1-phenyl-2-(p-rnethoxyphenyl) ethylene and methyl bromide, there was obtained the desired l-[p-(fi-diethylarninoethoxy)phenyl]-lphenyl 2 (p methoxyphenyhethylene methobrornide which melted at 205-208 C.

EXAMPLE IX 1- [17-(fl-diethylaminoe thoxy)phenyl] -Z- (p-tolyl) 2-(p-chl0r0phenyl) ethane ethobrom z'de When 1- [p-(fi-diethylaminoethoxy)phenyl] -1- (p-tolyl) Z-(p-chlorophenyl)ethane replaced the ethanol in the procedure of Example I there was obtained the desired l-[p- (fl-diethylaminoethoxy)phenyl] l-(p-tolyl)-2-(p-chlorophenyl)e=thane ethobromide, which melted with decomposition.

This application is a continuation-in-part of our copending application, Serial Number 676,478, filed August 6, 1957, now Patent No. 2,914,562.

4 We claim: 1. Compounds of the group consisting of those having the formula wherein R and R are lower alkyl radicals and R and R taken together with N form a heterocyclic amino radical selected from the group consisting of piperidino, morpholino, and pyrrolidinc, R is a lower alkyl radical, X is an anion selected from the group consisting of halogen, methosulfate, sulfate and toluenesulfate, n is an integer from two to three, (Y) is a radical selected from the group consisting of JGHz), ethylene ((I3=CH) and radicals, and R and R are selected from the group consisting of hydrogen lower alkyl, lower alkoxyl, halogen and perfiuorinated alkyl radicals with the proviso that R; and R cannot both be hydrogen.

2. 1 [p-(fi-diethylaminoethoxy)phenyl]-l-(p-tolyl)-2- (p-chlorophenyl ethanol ethobrornide.

3. 1-[p-(pi-diethyi-aminoethoxy)phenyl]-l-phenyl-2-(pmethoxyphenyl ethanol ethobromide 4. l-[p -(,B-dimethylarninoethoxy)phenyl]-1-(p-t0lyl)-2- (p-chlorophenyDethanol methobrornide 5. l-[p-(' -piperidinopropoxy)phenyl]-1-(p-chlorophenyl -2- (p-tolyl ethanol methobrornide 6. l-[p-(fl-diethylaminoethoxy)phenyl] l-(p-trifiuoromethylphenyl) -2-( pchlorophenyl) ethanol eth obromide 7. l-[p-(/fi-diethylarninoethoxy)phenyl] l-(p-tolyl)-2- (p-chlorophenyDethylene ethobrornide.

No references cited. 

1. COMPOUNDS OF THE GROUP CONSISTING OF THOSE HAVING THE FORMULA 